TY - JOUR
T1 - CNS disease-related protein variants as blood-based biomarkers in traumatic brain injury
AU - Williams, Stephanie M.
AU - Peltz, Carrie
AU - Yaffe, Kristine
AU - Schulz, Philip
AU - Sierks, Michael
N1 - Funding Information:
Study funded by the Department of Defense (W81XWH-14-1-0467).
Publisher Copyright:
© 2018 American Academy of Neurology
PY - 2018
Y1 - 2018
N2 - Objective: To utilize a panel of 11 single chain variable fragments (scFvs) that selectively bind disease-related variants of TAR DNA-binding protein (TDP)-43, β-amyloid, tau, and α-synuclein to assess damage following traumatic brain injury (TBI), and determine if the presence of protein variants could account for the increased risk of various neurodegenerative diseases following TBI. Methods: We utilized the panel of 11 scFvs in a sensitive ELISA format to analyze sera from 43 older veterans, 25 who had experienced at least 1 TBI incident during their lifetime (;29.4 years after TBI), and 18 controls who did not incur TBI, in a cross-sectional study. Results: Each of the 11 scFvs individually could significantly distinguish between TBI and control samples, though they did not detect each TBI sample. Comparing the levels of all 11 variants, all 25 TBI cases displayed higher reactivity compared to the controls and receiver operating characteristic analysis revealed 100% sensitivity and specificity. Higher total protein variants levels correlated with TBI severity and with loss of consciousness. Oligomeric tau levels distinguished between single and multiple TBI incidents. While all TBI cases were readily selected with the panel, the binding pattern varied from patient to patient, suggesting subgroups that are at increased risk for different neurodegenerative diseases. Conclusion: The panel of protein variants-specific scFvs can be used to identify blood-based biomarkers indicative of TBI even 20 years or more after the initial TBI. Being able to identify subgroups of biomarker profiles allows for the possibility of individually targeted treatments.
AB - Objective: To utilize a panel of 11 single chain variable fragments (scFvs) that selectively bind disease-related variants of TAR DNA-binding protein (TDP)-43, β-amyloid, tau, and α-synuclein to assess damage following traumatic brain injury (TBI), and determine if the presence of protein variants could account for the increased risk of various neurodegenerative diseases following TBI. Methods: We utilized the panel of 11 scFvs in a sensitive ELISA format to analyze sera from 43 older veterans, 25 who had experienced at least 1 TBI incident during their lifetime (;29.4 years after TBI), and 18 controls who did not incur TBI, in a cross-sectional study. Results: Each of the 11 scFvs individually could significantly distinguish between TBI and control samples, though they did not detect each TBI sample. Comparing the levels of all 11 variants, all 25 TBI cases displayed higher reactivity compared to the controls and receiver operating characteristic analysis revealed 100% sensitivity and specificity. Higher total protein variants levels correlated with TBI severity and with loss of consciousness. Oligomeric tau levels distinguished between single and multiple TBI incidents. While all TBI cases were readily selected with the panel, the binding pattern varied from patient to patient, suggesting subgroups that are at increased risk for different neurodegenerative diseases. Conclusion: The panel of protein variants-specific scFvs can be used to identify blood-based biomarkers indicative of TBI even 20 years or more after the initial TBI. Being able to identify subgroups of biomarker profiles allows for the possibility of individually targeted treatments.
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U2 - 10.1212/WNL.0000000000006322
DO - 10.1212/WNL.0000000000006322
M3 - Article
C2 - 30297502
AN - SCOPUS:85054776525
SN - 0028-3878
VL - 91
SP - 702
EP - 709
JO - Neurology
JF - Neurology
IS - 15
ER -